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Differential Genome Replication of a Unique Single-Amino-Acid Mutation in the Adenovirus-4 Component of the Live Oral Adenovirus Type 4 and Type 7 Vaccine

The FDA-approved Adenovirus Type 4 and Type 7 Vaccine, Live, Oral is highly effective and essential in preventing acute respiratory diseases (ARDs) in U.S. military recruits. Our study revealed the presence of a previously undetected mutation, not found in the wild-type human adenovirus type 4 (HAdV...

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Autores principales: Collins, Natalie D., Beaty, Shannon, Wallace, Elana, Li, Yuanzhang, Sanborn, Mark, Yang, Yu, Adhikari, Anima, Shabram, Paul, Warfield, Kelly, Karasavvas, Nicos, Kuschner, Robert A., Hang, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10385111/
https://www.ncbi.nlm.nih.gov/pubmed/37514960
http://dx.doi.org/10.3390/vaccines11071144
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author Collins, Natalie D.
Beaty, Shannon
Wallace, Elana
Li, Yuanzhang
Sanborn, Mark
Yang, Yu
Adhikari, Anima
Shabram, Paul
Warfield, Kelly
Karasavvas, Nicos
Kuschner, Robert A.
Hang, Jun
author_facet Collins, Natalie D.
Beaty, Shannon
Wallace, Elana
Li, Yuanzhang
Sanborn, Mark
Yang, Yu
Adhikari, Anima
Shabram, Paul
Warfield, Kelly
Karasavvas, Nicos
Kuschner, Robert A.
Hang, Jun
author_sort Collins, Natalie D.
collection PubMed
description The FDA-approved Adenovirus Type 4 and Type 7 Vaccine, Live, Oral is highly effective and essential in preventing acute respiratory diseases (ARDs) in U.S. military recruits. Our study revealed the presence of a previously undetected mutation, not found in the wild-type human adenovirus type 4 (HAdV-4) component of the licensed vaccine, which contains an amino acid substitution (P388T) in the pre-terminal protein (pTP). This study demonstrated that replication of the T388 HAdV-4 vaccine mutant virus is favored over the wild type in WI-38 cells, the cell type utilized in vaccine manufacturing. However, results from serial human stool specimens of vaccine recipients support differential genome replication in the gastrointestinal tract (GI), demonstrated by the steady decline of the percentage of mutant T388 vaccine virus. Since vaccine efficacy depends upon GI replication and the subsequent immune response, the mutation can potentially impact vaccine efficacy.
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spelling pubmed-103851112023-07-30 Differential Genome Replication of a Unique Single-Amino-Acid Mutation in the Adenovirus-4 Component of the Live Oral Adenovirus Type 4 and Type 7 Vaccine Collins, Natalie D. Beaty, Shannon Wallace, Elana Li, Yuanzhang Sanborn, Mark Yang, Yu Adhikari, Anima Shabram, Paul Warfield, Kelly Karasavvas, Nicos Kuschner, Robert A. Hang, Jun Vaccines (Basel) Article The FDA-approved Adenovirus Type 4 and Type 7 Vaccine, Live, Oral is highly effective and essential in preventing acute respiratory diseases (ARDs) in U.S. military recruits. Our study revealed the presence of a previously undetected mutation, not found in the wild-type human adenovirus type 4 (HAdV-4) component of the licensed vaccine, which contains an amino acid substitution (P388T) in the pre-terminal protein (pTP). This study demonstrated that replication of the T388 HAdV-4 vaccine mutant virus is favored over the wild type in WI-38 cells, the cell type utilized in vaccine manufacturing. However, results from serial human stool specimens of vaccine recipients support differential genome replication in the gastrointestinal tract (GI), demonstrated by the steady decline of the percentage of mutant T388 vaccine virus. Since vaccine efficacy depends upon GI replication and the subsequent immune response, the mutation can potentially impact vaccine efficacy. MDPI 2023-06-25 /pmc/articles/PMC10385111/ /pubmed/37514960 http://dx.doi.org/10.3390/vaccines11071144 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Collins, Natalie D.
Beaty, Shannon
Wallace, Elana
Li, Yuanzhang
Sanborn, Mark
Yang, Yu
Adhikari, Anima
Shabram, Paul
Warfield, Kelly
Karasavvas, Nicos
Kuschner, Robert A.
Hang, Jun
Differential Genome Replication of a Unique Single-Amino-Acid Mutation in the Adenovirus-4 Component of the Live Oral Adenovirus Type 4 and Type 7 Vaccine
title Differential Genome Replication of a Unique Single-Amino-Acid Mutation in the Adenovirus-4 Component of the Live Oral Adenovirus Type 4 and Type 7 Vaccine
title_full Differential Genome Replication of a Unique Single-Amino-Acid Mutation in the Adenovirus-4 Component of the Live Oral Adenovirus Type 4 and Type 7 Vaccine
title_fullStr Differential Genome Replication of a Unique Single-Amino-Acid Mutation in the Adenovirus-4 Component of the Live Oral Adenovirus Type 4 and Type 7 Vaccine
title_full_unstemmed Differential Genome Replication of a Unique Single-Amino-Acid Mutation in the Adenovirus-4 Component of the Live Oral Adenovirus Type 4 and Type 7 Vaccine
title_short Differential Genome Replication of a Unique Single-Amino-Acid Mutation in the Adenovirus-4 Component of the Live Oral Adenovirus Type 4 and Type 7 Vaccine
title_sort differential genome replication of a unique single-amino-acid mutation in the adenovirus-4 component of the live oral adenovirus type 4 and type 7 vaccine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10385111/
https://www.ncbi.nlm.nih.gov/pubmed/37514960
http://dx.doi.org/10.3390/vaccines11071144
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